A NEW multicentre study presented at ERA 2025 has uncovered three immunologically distinct subtypes of checkpoint inhibitor–induced acute interstitial nephritis (ICI-AIN), offering insights that may help personalise treatment strategies and predict patient outcomes.
In this retrospective analysis of 39 biopsy-confirmed ICI-AIN cases, researchers from multiple French institutions, including Hôpital Necker-Enfants Malades and the Cordeliers Research Center, performed multiplex immunofluorescence to profile kidney immune cell infiltrates. The study revealed three immune phenotypes, each associated with differing clinical courses and treatment responses.
Cluster 1 featured minimal mononuclear infiltration, while cluster 2 was dominated by T-cell–rich infiltrates and had the highest renal recovery rates at 12 months (100%). In contrast, cluster 3 was defined by a neutrophil-predominant profile with elevated C-reactive protein levels, greater proteinuria, and worse renal outcomes, only 34% of patients in this group achieved renal recovery. Relapse rates during corticosteroid tapering were also significantly higher in this group.
Importantly, the neutrophil-rich cluster showed a striking resemblance to acute pyelonephritis on histology, prompting further investigation into potential infectious causes and complement involvement. Metagenomic sequencing excluded infection, while urinary biomarker analysis identified elevated C5a levels and increased infiltration of C5aR1-expressing neutrophils—suggesting complement activation as a driver of this phenotype.
These findings not only reinforce the heterogeneity of ICI-AIN but also raise the possibility of immune phenotyping as a diagnostic and prognostic tool. With immune checkpoint inhibitors becoming a cornerstone in oncology, understanding the mechanisms behind renal immune-related adverse events could be key to delivering more targeted and effective nephro-oncological care.
Reference
Boudhabhay I et al. Immune Phenotyping of Checkpoint Inhibitor-Induced Acute Interstitial Nephritis Uncovers Distinct Profiles Associated with Clinico-biological Features, treatment Response and outcome. Abstract 1320. ERA Annual Meeting, 4th-7th June, 2025.
